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. 2020 Sep 9;4(7):1087–1110. doi: 10.1002/rth2.12420

TABLE 1.

Overview of sdAbs used in the thrombosis and hemostasis field

Target protein Camelid species/Synthetic library sdAb nomenclature Binding site Activity Application References
Antithrombin Llama KB‐AT‐01 ‐ 07; KB‐AT‐23 None defined Neutralization of antithrombin function Research/Therapy 79
Factor VIIa Llama αFVIIa‐VHH FVIIa protease domain Detection of FVIIa but not FVII Diagnostics 75
Factor VIIa Llama KB‐FVIIa‐004 FVIIa protease domain Inhibits free FVIIa but not TF‐bound FVIIa activity Research 49
Factor XIIa Llama A10 Catalytic domain Binds selectively to α‐FXIIa Research/Diagnostics 52
Factor XIIa Llama B7 Catalytic domain Binds both α‐FXIIa and β‐FXIIa Research/Diagnostics 52
Fibrinogen Dromedary VFIB1, ‐2, ‐3 None defined High‐affinity binding to fibrinogen Diagnostics 76, 77
PAI‐1 Alpaca VHH‐s‐a98 Surface loops around central β‐sheet A Switches PAI‐1/PA to substrate pathway Research 105
PAI‐1 Alpaca VHH‐2w‐64 (Nb64) Surface loops around central β‐sheet A Switches PAI‐1/PA to substrate pathway Research/Therapy 60, 105
PAI‐1 Alpaca VHH‐s‐a27 None defined Neutralization of PAI‐1 function Research 105
PAI‐1 Alpaca VHH‐s‐a93 Vicinity of reactive center loop Interferes with initial PAI‐1/PA complex formation Research 105
PAI‐1 Alpaca VHH‐2g‐42 (Nb42) Vicinity of reactive center loop Interferes with initial PAI‐1/PA complex formation Research/Therapy 60, 105
PN‐1 Synthetic library KB‐PN1‐A08, ‐B11, ‐F06, ‐H12 Reactive center loop Neutralization of human and murine PN‐1 function Research 106
hTAFI Alpaca VHH‐TAFI‐i and VHH‐TAFI‐a series None defined Interfere with TAFI activation and/or activity Research 54, 55, 57
hTAFI Alpaca

VHH‐TAFI‐a51

VHH‐TAFI‐i103

None defined Stimulate activity of TAFI zymogen Research 56
mTAFI Alpaca VHH‐TAFI‐i49 Lys212 & Arg227 Stimulates activity of TAFI zymogen Research 107
u‐PA Alpaca Nb4 Active site Inhibits u‐PA activity Research 59
u‐PA Alpaca Nb7 37s and 70s loops of the N‐terminal β‐barrel Allosteric inhibitor of u‐PA activity Research 58
u‐PA Alpaca Nb22 Active site Inhibits u‐PA activity Research 58
VWF Llama ALX‐0081 (caplacizumab) Human A1 domain Inhibition of VWF/glycoprotein Ibα interaction Therapy 80, 82, 83
VWF Llama KB‐VWF‐006bv Human/murine A1 domain Inhibition of VWF/glycoprotein Ibα interaction Research 63, 64
VWF Llama AU‐VWFa‐11 Human/murine A1 domain Specifically detects platelet‐binding VWF conformation Diagnostics 66, 67, 69, 72, 73, 74

Abbreviations: hTAFI, thrombin‐activatable fibrinolysis inhibitor; mTAFI, murine thrombin‐activatable fibrinolysis inhibitor; PA, plasminogen activator; PAI‐1, plasminogen activator inhibitor‐1; PN‐1, protease nexin‐1; u‐PA, urokinase plasminogen activator; TAFI, thrombin‐activatable fibrinolysis inhibitor; VWF, von Willebrand factor.